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171.
172.
The conformational state of Tes regulates its zyxin-dependent recruitment to focal adhesions 总被引:1,自引:0,他引:1 下载免费PDF全文
Garvalov BK Higgins TE Sutherland JD Zettl M Scaplehorn N Köcher T Piddini E Griffiths G Way M 《The Journal of cell biology》2003,161(1):33-39
The function of the human Tes protein, which has extensive similarity to zyxin in both sequence and domain organization, is currently unknown. We now show that Tes is a component of focal adhesions that, when expressed, negatively regulates proliferation of T47D breast carcinoma cells. Coimmunoprecipitations demonstrate that in vivo Tes is complexed with actin, Mena, and vasodilator-stimulated phosphoprotein (VASP). Interestingly, the isolated NH2-terminal half of Tes pulls out alpha-actinin and paxillin from cell extracts in addition to actin. The COOH-terminal half recruits zyxin as well as Mena and VASP from cell extracts. These differences suggest that the ability of Tes to associate with alpha-actinin, paxillin, and zyxin is dependent on the conformational state of the molecule. Consistent with this hypothesis, we demonstrate that the two halves of Tes interact with each other in vitro and in vivo. Using fibroblasts lacking Mena and VASP, we show that these proteins are not required to recruit Tes to focal adhesions. However, using RNAi ablation, we demonstrate that zyxin is required to recruit Tes, as well as Mena and VASP, but not vinculin or paxillin, to focal adhesions. 相似文献
173.
Olivares-Navarrete R Hyzy SL Chaudhri RA Zhao G Boyan BD Schwartz Z 《Biology of sex differences》2010,1(1):4-11
Background
Osseointegration depends on the implant surface, bone quality and the local and systemic host environment, which can differ in male and female patients. This study was undertaken in order to determine if male and female cells respond differently to titanium surfaces that have micron-scale roughness and if interactions of calciotropic hormones [1α,25(OH)2D3 and 17β-oestradiol (E2)] and microstructured surfaces on osteoblasts are sex dependent.Methods
Osteoblasts from 6-week old Sprague-Dawley rats were cultured on tissue culture polystyrene (TCPS) or on titanium (Ti) disks with two different surface topographies, a smooth pretreated (PT) surface and a coarse grit-blasted/acid-etched (SLA) surface, and treated with 1α,25(OH)2D3, E2, or E2 conjugated to bovine serum albumin (E2-BSA).Results
Male and female cells responded similarly to Ti microstructure with respect to cell number and levels of osteocalcin, transforming growth factor-β1, osteoprotegerin and prostaglandin E2 in their conditioned media, exhibiting a more differentiated phenotype on SLA than on PT or TCPS. E2 and E2-BSA increased differentiation and local factor production, an effect that was microstructure dependent and found only in female osteoblasts. 1α,25(OH)2D3 increased osteoblast differentiation and local factor production in female and male cells, but the effect was more robust in male cells.Conclusions
Male and female rat osteoblasts respond similarly to surface microstructure but exhibit sexual dimorphism in substrate-dependent responses to systemic hormones. Oestrogen affected only female cells while 1α,25(OH)2D3 had a greater effect on male cells. These results suggest that successful osseointegration in males and females may depend on the implant surface design and correct levels of calciotropic hormones. 相似文献174.
Hovering and dead individuals of the diurnal hawk-moth Macroglossum stellatarum (Linnaeus, 1758) (Lepidoptera: Sphingidae) were found with proboscides got stuck into flowers of the ornamental plant Oenothera speciosa Nutt (Onagraceae). The phenomenon was observed in several locations in Bulgaria where the plant has been introduced. Microscopic examination revealed that the reason for this unusual interaction is pubescence of thick-walled basiscopically oriented trichomes in the basal part of the hypanthium and style of the plant. When a foraging moth inserts its proboscis into this area, the tips of the trichomes are inserted into the transverse grooves of proboscis and hamper its back movement. As a result the moths are suspended for a long time, sometimes until death. Other trapped moth species were also observed but they always effected self-release. This plant–insect interaction is also a conservation issue as an estimation of its impact on wild insect populations is lacking. 相似文献
175.
176.
Tracy A. Denison Christopher F. Koch Irving M. Shapiro Zvi Schwartz Barbara D. Boyan 《Journal of cellular biochemistry》2009,107(1):155-162
Chondrogenic ATDC5 cells were used as a model of in vitro endochondral maturation to study the role of inorganic phosphate (Pi) in the regulation of growth plate chondrocytes by vitamin D3 metabolites. ATDC5 cells that were cultured for 10 days post‐confluence in differentiation media and then treated for 24 h with Pi produced a type II collagen matrix based on immunohistochemistry and expressed mRNAs for several chondrocytic markers, including aggrecan, collagen types II and X, cartilage oligomeric matrix protein, and SOX9. Pi also caused a decrease in [35S]‐sulfate incorporation and stimulated apoptosis, as evidenced by increased DNA fragmentation and caspase‐3 activity. In addition, treatment with Pi induced sensitivity to 24,25‐dihydroxyvitamin D3 and this effect was both dose‐dependent and was blocked by phosphonoformic acid (PFA), a specific inhibitor of sodium dependent type III Pi transporters. Treatment with 24R,25(OH)2D3 reduced cell number and increased alkaline phosphatase specific activity in a dose‐dependent manner. Moreover, 24R,25(OH)2D3 reversed the Pi‐induced decrease in incorporation of [3H]‐thymidine and [35S]‐sulfate incorporation, as well as the Pi‐induced increase in apoptosis. These results suggest that Pi acts as an early chondrogenic differentiation factor, inducing response to 24R,25(OH)2D3; treatment of committed chondrocytes with Pi induces apoptosis, but 24R,25(OH)2D3 mitigates these effects, indicating a possible inhibitory feedback loop. J. Cell. Biochem. 107: 155–162, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
177.
Hyzy SL Olivares-Navarrete R Schwartz Z Boyan BD 《Journal of cellular biochemistry》2012,113(10):3236-3245
Large doses of bone morphogenetic protein 2 (BMP2) are used clinically to induce bone formation in challenging bone defects. However, complications after treatment include swelling, ectopic bone formation, and adjacent bone resorption. While BMP2 can be effective, it is important to characterize the mechanism of the deleterious effects to optimize its use. The aim of this study was to determine the effect of BMP2 on apoptosis in osteoblast lineage cells and to determine the role of the BMP inhibitor Noggin in this process. Human mesenchymal stem cells (MSCs), immature osteoblast‐like MG63 cells, and mature normal human osteoblasts (NHOst) were treated with BMP2. A model system of increased endogenous BMP signaling was created by silencing Noggin (shNOG‐MG63). Finally, the BMP pathway regulating apoptosis in NHOst was examined using BMP signaling inhibitors (5Z‐7‐oxozeaenol, dorsomorphin, H‐8). Apoptosis was characterized by caspase‐3, BAX/BCL2, p53, and DNA fragmentation. BMP2 induced apoptosis in a cell‐type dependent manner. While the effect was minor in MSCs, MG63 cells had modest increases and NHOst cells had robust increases apoptosis after BMP2 treatment. Apoptosis was significantly higher in shNOG‐MG63 than MG63 cells. 5Z‐7‐oxozeaenol and dorsomorphin eliminated the BMP2‐induced increase in DNA fragmentation in NHOst, suggesting roles for TAB/TAK1 and Smad signaling. These results indicate that the apoptotic effect of BMP2 is dependent on cell maturation state, inducing apoptosis in committed osteoblasts through Smad and TAB/TAK1 signaling, and is regulated by Noggin. Dose and delivery must be optimized in therapeutic applications of BMP2 to minimize complications. J. Cell. Biochem. 113: 3236–3245, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
178.
Yuk IH Zhang B Yang Y Dutina G Leach KD Vijayasankaran N Shen AY Andersen DC Snedecor BR Joly JC 《Biotechnology and bioengineering》2011,108(11):2600-2610
Protein glycation is a non-enzymatic glycosylation that can occur to proteins in the human body, and it is implicated in the pathogenesis of multiple chronic diseases. Glycation can also occur to recombinant antibodies during cell culture, which generates structural heterogeneity in the product. In a previous study, we discovered unusually high levels of glycation (>50%) in a recombinant monoclonal antibody (rhuMAb) produced by CHO cells. Prior to that discovery, we had not encountered such high levels of glycation in other in-house therapeutic antibodies. Our goal here is to develop cell culture strategies to decrease rhuMAb glycation in a reliable, reproducible, and scalable manner. Because glycation is a post-translational chemical reaction between a reducing sugar and a protein amine group, we hypothesized that lowering the concentration of glucose--the only source of reducing sugar in our fed-batch cultures--would lower the extent of rhuMAb glycation. When we decreased the supply of glucose to bioreactors from bolus nutrient and glucose feeds, rhuMAb glycation decreased to below 20% at both 2-L and 400-L scales. When we maintained glucose concentrations at lower levels in bioreactors with continuous feeds, we could further decrease rhuMAb glycation levels to below 10%. These results show that we can control glycation of secreted proteins by controlling the glucose concentration in the cell culture. In addition, our data suggest that rhuMAb glycation occurring during the cell culture process may be approximated as a second-order chemical reaction that is first order with respect to both glucose and non-glycated rhuMAb. The basic principles of this glycation model should apply to other recombinant proteins secreted during cell culture. 相似文献
179.
基于地理种源的刨花楠苗木比叶面积与叶片化学计量学关系 总被引:1,自引:0,他引:1
探讨植物比叶面积(SLA)与叶片碳(C)、氮(N)、磷(P)化学计量学关系,能够反映植物为获取最大光合生产所采取的内部调控机制,共同体现植物的适应策略。利用生长于同一土壤与气候环境中培育的刨花楠(Machilus pauhoi)1年生苗木,对其SLA与叶片C、N、P含量进行测定,并对SLA与叶片C、N、P化学计量学特征及其与种源地环境因子的关系进行分析。结果表明:(1)叶片养分含量的变异系数大小排序为CNP;SLA与叶片N、P含量呈显著的正相关,与叶片C∶N及C∶P呈极显著的负相关。(2)SLA与经度、年均温、年降水量呈显著负相关;叶片C、N、P含量也受种源地环境因子影响,其中以海拔最为重要。研究结果有助于理解刨花楠苗木的生存适应对策,对探究刨花楠对养分的资源利用效率等具有重要意义。 相似文献
180.
Sperm surface galactosyltransferase activities during in vitro capacitation 总被引:3,自引:7,他引:3 下载免费PDF全文
Studies using genetic and biochemical probes have suggested that mouse sperm surface galactosyltransferases may participate during fertilization by binding N- acetylglucosamine (GlcNAc) residues in the egg zona pellucida. In light of these results, we examined sperm surface galactosyltransferase activity during in vitro capacitation to determine whether changes in enzymatic activity correlated with fertilizing ability. Results show that surface galactosyltransferases on uncapacitated sperm was preferentially loaded with poly N-acetyllactosamine substrates. As a consequence of capacitation in Ca(++)-containing medium, these polylactosaminyl substrates are spontaneously released from the sperm surface, thereby exposing the sperm galactosyltransferase for binding to the zona pellucida. Sperm capacitation can be mimicked, in the absence of Ca(++), either by washing sperm in Ca(++)-free medium, or by pretreating sperm with antiserum that reacts with the galactosyltransferase substrate. In both instances, sperm galgactosylation of endogenous polylactosaminyl substrates is reduced, coincident with increased galactosylation of exogenous GlcNAc, and increased binding to the zona pellucida. Binding of capacitated sperm to the egg can be inhibited by pronase-digested high molecular weight polyactosaminyl glycoside extracted from epidymal fluids or from undifferentiated F9 embryonal carninoma cells. Thus, these glycosides function as “decapacitation factors” when added back to in vitro fertilization assays. These glycoside “decapacitation factors” inhibit sperm-egg binding by competeing for the sperm surface galactosyltransferase, since (a) they are galactosylated by sperm in the presence of UDP[(3)H]galactose, and (b) enzymatic removal of terminal GlcNAc residues reduces “decapacitation factio” competition. On the other hand “conventional” low molecular weight glycosides, isolated from either epididymal fluid or differentiated F9 cells, fail to inhibit capacitated sperm binding to the zona pellucida. These results define a molecular mechanism for one aspect of sperm capacitation, and help explain why removal of “decapacitation factos” is a necessary prerequisite for sperm binding to the zona pellucida. 相似文献